Gallstones - Causes, Pathogenesis, Signs & Symptoms, Complications, Diagnosis & Treatment

gallstones are hard solid masses that are formed in the biliary tract usually in the gallbladder coleothesis is the medical term used for gallstone disease gallstones usually develop insidiously and they may remain asymptomatic for decades prevalence of gallstone disease is higher in western countries like america and europe compared to asia and africa women are more likely to develop gallstones especially in their reproductive age and the risk of gallstone disease increases with age gallstone disease is uncommon in children in the absence of congenital abnormalities or hemolytic disorders bile is produced inside the liver and secreted into the biliary tree here is a diagram of the biliary tree bile produced in the liver is secreted into the right and left hepatic ducts and then into the common hepatic duct gallbladder is joined to the common hepatic duct via the cystic duct the main function of gallbladder is to store excess bile within union of the common hepatic duct and the cystic duct forms the common bile duct which continues downwards to drain into the second part of the duodenum at the ampulla of waiter pancreatic duct also joins the common bile duct just above the ampulla of waiter now let's discuss about the pathophysiology of gallstone disease two main substances are involved in the formation of gallstones cholesterol and calcium bilirubinate gallstone formation occurs when the concentrations of these substances exceed their solubility in bile which is known as supersaturation when bile is supersaturated with these substances they precipitate from the solution as microscopic crystals these microscopic crystals are trapped in the gallbladder mucus producing gallbladder sludge over time these tiny crystals grow aggregate and fuse to form macroscopic stones occlusion of the ducts by the gallbladder sludge or stones produce complications of gallstone disease here is a gross image of gallstones within the gallbladder more than 80 percent of gallstones contain cholesterol as their major component liver cells secrete cholesterol into the bile along with the phospholipid lecithin in the form of small spherical bubbles called unilamelar vesicles in these vesicles one lecithin molecule holds up to one cholesterol molecule liver cells also secrete bile salts which are essentially required for the absorption of dietary fat in the small intestine and these bile salts dissolve the unilamelar vesicles within the gallbladder to form mixed micelles these micelles have a lower cholesterol carrying capacity than unilamal or vesicles therefore the amount of free cholesterol molecules is higher within the gallbladder in addition in the gallbladder water and electrolyte in the bile are reabsorbed into the blood which causes concentration of bile so secretion of high amounts of cholesterol by the liver may lead to super saturation of bile with cholesterol so the two major factors that determine the formation of cholesterol stones are the amount of cholesterol secreted by the liver cells relative to lecithin and bile salts and the degree of concentration and the extent of stasis of bile within the gallbladder calcium bilirubinate and pigment gallstones are relatively less common than cholesterol gallstones bilirubin is a yellow pigment derived from the breakdown of heme and is actively secreted into the bile by liver cells in the bloodstream bolirobin is in its unconjugated form once liver cells take up these unconjugated bilirubin molecules they add a glucuronic acid molecule to each bilirubin molecule to form conjugated bolerobium conjugated bolerobin is water-soluble and stable however a small amount of bilirubin is excreted into the bile in the unconjugated form this unconjugated bilirubin tends to form insoluble precipitates with calcium and bile in conditions with high heme turnover such as chronic hemolysis and cirrhosis high amounts of unconjugated bilirubin are excreted in bile which enhances their precipitation along with calcium leading to the formation of calcium bilirubinate crystals then these crystals aggregate and form gallstones over time various oxidation processes cause these stones to take a black color stones formed in this manner are called black pigment gallstones bile is normally sterile but in some unusual circumstances such as in biliary strictures where the flow of bile is obstructed it may become colonized with bacteria these bacteria hydrolyze conjugated bilirubin to form unconjugated bilirubin which may increase the tendency of calcium bilirubinate gallstone formation in addition these bacteria hydrolyze the lecithin component in bile which releases large amounts of free fatty acids similar to unconjugated bilirubin fatty acids also bind to calcium and precipitate along with calcium bilirubinate stones formed in this manner are called brown pigment gallstones unlike other types brown pigment gallstones are more common in parts of southeast asia there is another type of gallstones called mixed gallstones when cholesterol stones become colonized with bacteria they elicit an inflammatory reaction in the gallbladder mucosa lytic enzymes secreted by the inflammatory cells hydrolyze conjugated bilirubin and lecithin so the cholesterol stones may accumulate calcium bilirubinate and other calcium salts forming mixed gallstones larger stones that are formed in this manner may develop a rim of calcium resembling an egg shell that is visible on a plain x-ray film now let's discuss about the causes of gallstone disease as different types of gallstones have different pathogenesis their etiology also differ from each other causes for cholesterol gallstones include the following obesity obesity is associated with metabolic syndrome insulin resistance hyperlipidemia and type 2 diabetes in all of these conditions liver secretes high amounts of cholesterol in bile which increases the risk of developing gallstones multiple pregnancies is another cause major contributing factor is the high progesterone levels during pregnancy progesterone reduces the contractility of gallbladder which leads to prolonged retention and greater concentration of bile within other causes of gallbladder stasis include spinal cord injuries which also reduces the gallbladder contractility prolonged fasting with total parenteral nutrition which decreases the enteric stimulation of gallbladder contraction and rapid weight loss associated with severe caloric and fat restriction by diet or gastric bypass surgery some medications also induce the formation of gallstones in some individuals some of these drugs include estrogen which is used for contraception in women or treatment of prostate cancer in men estrogen increases the risk of gallstone formation by increasing biliary excretion of cholesterol another type of drugs is fibrates these drugs also increase the biliary excretion of cholesterol somatostatin analogues also increase the risk of gallstone formation by decreasing gallbladder emptying genetics also plays a role in gallstone disease in approximately 25 percent of patients formation of calcium bilirubinate gallstones occurs in individuals with high heme turnover disorders of increased hemolysis include the following sickle cell disease hereditary spherocytosis beta thalassemia and cirrhosis in cirrhosis portal hypertension leads to splenomegaly this in turn causes red cell sequestration leading to a moderate increase in hemoglobin turnover for brown pigment stones to form there should be stasis of bile within the duct system along with chronic colonization of bacteria common conditions which favors the formation of brown pigment gallstones include post-operative biliary stricture cyst and liver fluke infestation other causes of gallstone disease include crohn's disease and allele resection which decreases the absorption of bile salts burns paralysis prolonged icu care and major trauma now let's discuss about the clinical presentation of gallstone disease gallstone disease usually has following four stages lithogenic state in which certain conditions favor gallstone formation as we have discussed earlier asymptomatic gallstones symptomatic gallstones characterized by episodes of biliary colic and complicated gallstones symptoms and complications of gallstone disease occur when gallstones escape the gallbladder to lodge in the duct system of the biliary tree asymptomatic gallstones may be present in the gallbladder for decades without causing any symptoms of complications most of these gallstones are discovered incidentally biliary colic is the term used to describe the pain caused by gallstones this pain occurs when gallstones or sludge unexpectedly impact in the cystic duct during gallbladder contraction increasing the gallbladder wall tension pain is usually felt in the right upper quadrant and epigastric region and may radiate to the tip of the right scapula which is known as the collins sign episodes of biliary colic are infrequent and unpredictable the pain begins postprandially usually within an hour after a fatty meal and is often described as intense and dull an episode of biliary colic typically resolves within 30 to 90 minutes when the gallbladder stops contracting and the stone falls back into the gallbladder the pain is usually constant and is not relieved by emesis antacids defecation or positional changes and it may be associated with intense sweating nausea and vomiting other symptoms associated with gallstones include indigestion bloating and fat intolerance which are non-specific gallstone disease is associated with several complications acute challenges titus or inflammation of the gallbladder is one of the major complications it occurs when gallstones persistently impact the cystic duct causing gallbladder to become distended and inflamed patients experience the pain of biliary colic instead of resolving spontaneously this pain persists and worsens over time acute callicitis is considered a surgical emergency although inflammation may subside with conservative measures such as hydration and antibiotic therapy overgrowth of colonizing bacteria in the gallbladder is another complication and in severe cases accumulation of pus in the gallbladder termed gallbladder impima occurs in some cases gallbladder wall may become necrotic resulting in perforation and pericholecistic abscesses chronic cholecystitis occurs when persistent gallstones leads to chronic inflammation in the gallbladder this may ultimately lead to progressive fibrosis and loss of function of the gallbladder wall gallbladder carcinoma is an uncommon cancer which usually develops in the setting of gallstones and chronic cholestitis gallbladder cancers commonly invade the liver and common bile duct producing jaundice prognosis of gallbladder cancer is poor unless it is localized to the gallbladder cholecystoenteric fistula is a rare complication of gallstone disease it occurs when a large stone erodes through the gallbladder wall into the duodenum as you can see in this picture if the stone is sufficiently large it can obstruct the small intestine usually at the level of the ileum this condition is known as gallstone alias gall stones that are lodged in the common bile duct may also cause certain complications in some individuals gallstones are initially retained in the gallbladder by the spiral valves of the cystic duct with repeated impaction of gallstones these valves may become obliterated and stones may pass into the common bile duct patients who passed one stone tend to pass more stones over the subsequent months stones in the common bile duct may be asymptomatic but more commonly they impact distally the amulet of waiter this may produce biliary colic which is indistinguishable from that caused by cystic duct stones because common bile duct stones occlude the flow of bile increased pressure within the intra-hepatic bile ducts lead to elevated liver enzyme levels and jaundice bacterial overgrowth in stagnant bile above the obstruction can lead to purulent inflammation of the biliary tree in the liver a condition known as ascending cholangitis characteristic features are fever jaundice and right upper quadrant pain also known as the charcot triad patients may rapidly develop septic shock if the obstruction is not relieved as soon as possible the stone impacted at the ampulla of waiter may transiently obstruct the pancreatic duct leading to in situ activation of pancreatic proteases causing acute pancreatitis now let's discuss about the diagnosis of gallstone disease symptomatic gallstones clinically manifest as biliary colic as we have discussed earlier however they are unlikely to be associated with significant abnormalities of laboratory investigations abdominal ultrasound scan is the single most useful investigation to diagnose gallstone disease in addition acute cholecystitis is usually associated with moderate leukocytosis and raised inflammatory markers such as c reactive proteins serum bilirubin alp and amino transfers levels may be marginally elevated in the presence of cholecystitis alone in common bile duct obstruction there will be more significant elevation of serum bilirubin alp and gamma glutamal transfers levels along with elevated ceramic levels with prolonged obstruction the absorption of lipid soluble vitamins from the gut will be reduced including vitamin k which is essential for the synthesis of several clotting factors this will ultimately lead to prolonged prothrombin time finally let's discuss about the treatment of gallstone disease asymptomatic gallstone disease usually does not need any treatment unless it becomes symptomatic cholecystectomy is the treatment of choice for virtually all patients with symptomatic gallbladder stones laperoscopic cholecystectomy is the most preferred method because it has many benefits over open cholecystectomy in addition pure and near pure cholesterol gallstones can be dissolved by increasing the bile salt content of bile by giving oral agents like urso deoxycolic acid however this requires long-term therapy and the recurrence of gallstones is high when therapy is stopped additional pharmacological agents for treating cholesterol gallstones include statins to inhibit hepatic cholesterol synthesis and is edamame which reduces the intestinal absorption of cholesterol extracorporeal shockwave lithotripsy is a newer method to break larger gallstones into small fragments using ultrasound waves then the small gallstone fragments will be passed down through the common bile duct during gallbladder contraction acute callicistitis should be managed initially with conservative therapy this includes keeping the patient nil by mouth while administering intravenous fluids opioid analgesics and intravenous antibiotics the effective antibiotic options include extended spectrum cephalosporins along with metronidazole and piparacyline or emitting them these antibiotic options may vary depending on the geographic region and it would be better if you refer the local guidelines for the management of acute cholecystitis cholecystectomy is usually delayed to allow the symptoms to be settled